WO2012100083A3 - Human induced neuronal cells - Google Patents

Human induced neuronal cells Download PDF

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Publication number
WO2012100083A3
WO2012100083A3 PCT/US2012/021910 US2012021910W WO2012100083A3 WO 2012100083 A3 WO2012100083 A3 WO 2012100083A3 US 2012021910 W US2012021910 W US 2012021910W WO 2012100083 A3 WO2012100083 A3 WO 2012100083A3
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WO
WIPO (PCT)
Prior art keywords
human induced
hin
fibroblast
induced neuronal
neuronal cells
Prior art date
Application number
PCT/US2012/021910
Other languages
French (fr)
Other versions
WO2012100083A2 (en
Inventor
Asa Abeliovich
Liang QIANG
Original Assignee
The Trustees Of Columbia University In The City Of New York
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Trustees Of Columbia University In The City Of New York filed Critical The Trustees Of Columbia University In The City Of New York
Priority to US13/980,832 priority Critical patent/US20140193341A1/en
Publication of WO2012100083A2 publication Critical patent/WO2012100083A2/en
Publication of WO2012100083A3 publication Critical patent/WO2012100083A3/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0619—Neurons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
    • A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5058—Neurological cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/13—Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/60—Transcription factors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/13—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells
    • C12N2506/1307—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from adult fibroblasts
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2510/00—Genetically modified cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/30—Synthetic polymers
    • C12N2533/32—Polylysine, polyornithine
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G01N2800/2814—Dementia; Cognitive disorders
    • G01N2800/2821—Alzheimer

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Neurology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Organic Chemistry (AREA)
  • Toxicology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Neurosurgery (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • General Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Rheumatology (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

A method for reprogramming a fibroblast into a human induced neuronal cell (hIN) is described. The method comprises expressing heterologous reprogramming factors Bm2, Myt11, Zicl, Olig2, Asc11 or any combination thereof, in said fibroblast, and culturing the fibroblast in a medium comprising BDNF, NT3, GeM or any combination thereof. Biomarkers describing the obtained hiN cells are also presented. In another aspect, methods for screening compounds using the hiN cells is described.
PCT/US2012/021910 2011-01-19 2012-01-19 Human induced neuronal cells WO2012100083A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US13/980,832 US20140193341A1 (en) 2011-01-19 2012-01-19 Human induced neuronal cells

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201161434190P 2011-01-19 2011-01-19
US61/434,190 2011-01-19
US201161505407P 2011-07-07 2011-07-07
US61/505,407 2011-07-07

Publications (2)

Publication Number Publication Date
WO2012100083A2 WO2012100083A2 (en) 2012-07-26
WO2012100083A3 true WO2012100083A3 (en) 2012-09-20

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2012/021910 WO2012100083A2 (en) 2011-01-19 2012-01-19 Human induced neuronal cells

Country Status (2)

Country Link
US (1) US20140193341A1 (en)
WO (1) WO2012100083A2 (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6335117B2 (en) * 2012-03-21 2018-05-30 国立大学法人京都大学 Method for screening therapeutic and / or prophylactic agent for Alzheimer's disease
US9730975B2 (en) 2014-11-25 2017-08-15 The Penn State Research Foundation Chemical reprogramming of human glial cells into neurons for brain and spinal cord repair
US11027047B2 (en) 2015-03-31 2021-06-08 The University Of North Carolina At Chapel Hill Delivery vehicles for stem cells and uses thereof
US20200123499A1 (en) * 2015-12-02 2020-04-23 Massachusetts Institute Of Technology Method for efficient generation of neurons from non-neuronal cells
WO2017223052A1 (en) * 2016-06-20 2017-12-28 The Board Of Trustees Of The Leland Stanford Junior University Biologically relevant in vitro screening of human neurons
US20200377885A1 (en) * 2017-08-07 2020-12-03 Washington University Compositions and methods for the generation of neurons and uses thereof
KR102203860B1 (en) * 2019-05-24 2021-01-15 주식회사 아이피에스바이오 Induced pluripotent stem cells having presenilin protein mutants(E120K) derived from Alzheimer's disease patients
WO2023283577A1 (en) * 2021-07-06 2023-01-12 Washington University Compositions and methods for the generation of neurons and uses thereof
WO2023039503A2 (en) * 2021-09-10 2023-03-16 Alnylam Pharmaceuticals, Inc. App irna compositions and methods of use thereof for treating or preventing diseases characterized by enlarged endosomes

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2000479A1 (en) * 1995-04-28 2008-12-10 HSC Research and Development Limited Partnership Genetic Sequences and Proteins Related to Alzheimer's Disease, and Uses Therefor
US7632680B2 (en) * 2001-08-08 2009-12-15 Levesque Biosciences, Inc. Compositions and methods for isolation, propagation, and differentiation of human stem cells and uses thereof
US20100167286A1 (en) * 2008-06-24 2010-07-01 Parkinson's Institute Pluripotent cell lines and methods of use thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2000479A1 (en) * 1995-04-28 2008-12-10 HSC Research and Development Limited Partnership Genetic Sequences and Proteins Related to Alzheimer's Disease, and Uses Therefor
US7632680B2 (en) * 2001-08-08 2009-12-15 Levesque Biosciences, Inc. Compositions and methods for isolation, propagation, and differentiation of human stem cells and uses thereof
US20100167286A1 (en) * 2008-06-24 2010-07-01 Parkinson's Institute Pluripotent cell lines and methods of use thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KIM ET AL.: "Robust enhancement of neural differentiation from human ES and iPS cells regardless of their innate difference in differentiation propensity", STEM CELL REV., vol. 6, no. 2, June 2010 (2010-06-01), pages 270 - 281, XP055007831, DOI: doi:10.1007/s12015-010-9138-1 *
VIERBUCHEN ET AL.: "Direct conversion of fibroblasts to functional neurons by defined factors", NATURE, vol. 463, no. 7284, 25 February 2010 (2010-02-25), pages 1035 - 1041, XP055023150, DOI: doi:10.1038/nature08797 *

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Publication number Publication date
US20140193341A1 (en) 2014-07-10
WO2012100083A2 (en) 2012-07-26

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